F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening

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金黄色葡萄球菌RNaseH Ⅰ、RNaseH Ⅱ和RNaseH Ⅲ突变菌株的构建及功能研究

目的:在金黄色葡萄球菌中分别构建RNaseHⅠ、RNaseHⅡ和RNaseHⅢ的突变菌株,并研究它们在金黄色葡萄球菌中的生物学功能。方法:利用同源重组的方法在金黄色葡萄球菌中分别构建RNaseHⅠ、RNaseHⅡ和RNaseHⅢ的插入突变菌株,检测突变株生长速度、溶血活性及外分泌蛋白表达水平与野生型的差异,进一步通过流式细胞术检测突变株外分泌蛋白细胞毒性的改变,同时在体外检测突变株在全血中的存活能力。结果:构建了金黄色葡萄球菌RNaseHⅠ、RNaseHⅡ和RNaseHⅢ的插入突变菌株;表型检测结果显示,与野生型菌株相比,3种突变株的生长速度减慢,溶血素和外分泌蛋白明显减少;流式细胞术检测结果显示3种突变株毒性比野生型菌株减弱;全血杀伤实验结果显示3种突变株在全血中的存活率低于野生型菌株。结论:RNaseHⅠ、RNaseHⅡ和RNaseHⅢ在金黄色葡萄球菌生长繁殖、毒素产生和侵袭机体的过程中有重要作用,它们可能与金黄色葡萄球菌的致病性相关。     

Identification of two HIV inhibitors that also inhibit human RNaseH2

A total of 140,000 compounds were screened in a targetfree cell-based high throughput assay against HIV-1 infection, and a subset of 81 promising compounds was identified. Secondary screening of these 81 compounds revealed two putative human RNaseH2 inhibitors, RHI001 and RHI002, with IC50 value of 6.8 μM and 16 μM, respectively. RHI002 showed selective activity against human RNaseH2 while RHI001 inhibited HIV-RNaseH, E. coli RNaseH, and human RNaseH1 with IC50 value of 28.5 μM, 7.9 μM, and 31.7 μM, respectively. Kinetic analysis revealed that both inhibitors had non-competitive inhibitor-like properties. Because RNaseH2 is involved in the etiology of Aicardi-Goutier syndrome and has been suggested as an anticancer drug target, small molecule inhibitors modulating its activity would be useful for investigating the cellular function of this molecule.     

TERRA and RAD51AP1 promote alternative lengthening of telomeres through an R- to D-loop switch

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Locked nucleic acids (LNA) and medical applications

Summary Locked Nucleic Acid (LNA) is a novel, third generation DNA analogue that has the potential to impact strongly on the future development of a diversity of nucleic acid based technologies. The present chapter reviews the known biochemical properties of LNA and exemplifies how these have been used to improve both DNA diagnostic technologies and antisense therapeutics.     

Locked nucleic acids (LNA) and medical applications

Locked Nucleic Acid (LNA) is a novel, third generation DNA analogue that has the potentialto impact strongly on the future development of a diversity of nucleic acid based technologies.The present chapter reviews the known biochemical properties of LNA and exemplifies how thesehave been used to improve both DNA diagnostic technologies and antisense therapeutics.     

Locked nucleic acids (LNA) and medical applications

Summary Locked Nucleic Acid (LNA) is a novel, third generation DNA analogue that has the potential to impact strongly on the future development of a diversity of nucleic acid based technologies. The present chapter reviews the known biochemical properties of LNA and exemplifies how these have been used to improve both DNA diagnostic technologies and antisense therapeutics.